VascuBone project develops toolbox for personalised bone regeneration

17 November 2014

The EU-funded VascuBone project has developed a "toolbox" that doctors can select from to regenerate bone for three types of bone defects. The tool box includes a variety of biocompatible biomaterials and cell types, FDA-approved growth factors, material modification technologies, simulation and analytical tools such as molecular-imaging-based in vivo diagnostics. These can all be combined for the specific medical needs of the patient.

Bone is one of the most frequently transplanted tissues and the demand is rising. Transplants treat large defects like those caused by trauma, complicated fractures, tumour resection or osteoporosis. Conventionally, a piece of bone is transferred from one body site to another of the same patient. But this has the disadvantage of causing a defect in an otherwise healthy part of the body. Using bone obtained from a donor also has side effects, such as immunogenic reactions. New methods are thus needed to meet the growing demand. The tools developed and optimised in the project are aimed at helping to overcome these existing shortcomings.

The project is due to complete in December 2014, when it will be holding its final meeting to report the latest achievements. In the previous year of the project researchers tested the biocompatibility of CeraSorb scaffolds (a tricalcium phosphate preparation) modified by hydrophilic diamond particles and polyester co-polymer scaffolds developed by the consortium and modified by nano diamond particles.

For evaluating the biomaterials, the project developed various MRI contrast agents based on fluorine compounds, a Gadolinium-based polymer and superparamagnetic iron oxide (SPIO) nanoparticles. These provide information on the structure of the scaffolds and blood flow in regenerating bone and biomaterials.

The project also developed a sensitive and non-invasive method for screening the tumorigenic potential of the scaffolds intended for bone regeneration using high potency bioluminescence (BLI) in vivo imaging.

“We would like to include everything in our toolbox that is necessary to put together the ideal therapy for a patient”, says project coordinator Heike Walles, Professor of Tissue Engineering and Regenerative Medicine at the University Hospital of Würzburg and also head of the Oncology Group at the Fraunhofer Institute IGB in Würzburg, Germany.

Walles previously developed a three-dimensional scaffold derived from a piece of pig bowel that contains structures supporting the development of blood vessels. Different types of adult stem cells, for example, so-called mesenchymal cells derived from bone marrow, are supposed to grow on such scaffolds to form the bone substitute.

"These cells are even present in old people,” Walles tells While the cells’ potential decreases with age, “they are still there and are able to regenerate“, she explains. “But they have to be enriched, which is increasingly difficult with increasing age,” she continued.

In the current project, researchers therefore analysed how age influences the stem cells’ properties. They identified markers that indicate whether the cells are suited for therapeutic use. They also looked at other types of cells, so-called endothelial cells. These may be necessary for treating very large bone defects.

“We analysed which cell type is ideal for therapeutic purposes, such as microvascular endothelial cells or endothelial progenitor cells, a stem cell type that can be found in the blood”, said Walles.

Cornelia Kasper, professor for biopharmaceutical technology at the University of Natural Resources and Life Sciences in Vienna, Austria, welcomes the toolbox approach: "It offers a combination of matrix, cells, bioreactors and automated systems, which can be used to grow tissue under controlled conditions."

Researchers "look for biological alternatives to screws, nails and titanium plates, particularly for treating defects larger than three centimetres," she said. Providing scaffolds with vessel structures for regenerating large bone defects is "something special and unique," she added.

Kaspar believes using stem cells from the patient’s own fat tissue or bone marrow and from the umbilical cord offer a huge potential for bone regeneration and has various advantages. "Particularly, mesenchymal stem cells are easily accessible," she said. There are no ethical concerns attached to using such cells and there are no immunogenic side effects. What is more, these cells exist in everyone. “Even slim or old patients have fat tissue,” she added.

She also hoped that such engineering based solutions will be more widely approved and available for patients within the next five to ten years. In her view, it is up to politics and the regulation authorities “to create the prerequisites for a comprehensive patient care“. But the cooperation between life scientists, engineers and medical scientists "still remains a real challenge", she concluded.

Heike Walles, discusses the project aims.

Further information

The VascuBone Project:

Source: Based on article on Healing bone defects using regenerative medicine


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